tbuckley/cabot-search huggingface dataset:
Choice of PD-L1 immunohistochemistry assay influences clinical eligibility for gastric cancer immunotherapy.
Authors: Ryan Yong Kiat Tay, Joe Poh Sheng Yeong, Jeffrey Lum, Chong Boon Teo, Benjamin Kye Jyn Tan, Yiong Huak Chan, Joan RE Choo, Anand Jeyasekhran, Qing Hao Miow, Lit-Hsin Loo, Wei-Peng Yong, Raghav Sundar
Journal: Journal of Clinical Oncology (2022)

4026 Background: Immune checkpoint inhibitors (ICI) are now standard-of-care treatment for patients with metastatic gastric cancer (GC). To guide patient selection for ICI therapy, programmed death ligand-1 (PD-L1) biomarker expression is routinely assessed via immunohistochemistry (IHC). Regulatory approval for ICIs is granted based on PD-L1 expression status, scored using metrics such as the combined positive score (CPS). However, with an increasing number of approved ICIs, each paired with a different PD-L1 antibody IHC assay used in their respective landmark trials, there is an unmet clinical and logistical need for harmonization. We thus investigated the interchangeability between the Dako 22C3, Dako 28-8 and Ventana SP-142 assays in GC PD-L1 IHC. Methods: In this cross-sectional study, samples were obtained via biopsy or resection of gastric cancer at the National University Hospital, Singapore. We scored 362 GC samples for PD-L1 CPS, tumor proportion score (TPS) and immune cells (IC) using a multiplex immunohistochemistry/immunofluorescence technique. 344 samples were developed into a tissue microarray (TMA), while 18 samples were used as whole slides for orthogonal validation. The samples selected for whole slide analysis were obtained from GC patients treated with ICI therapy. Results: The percentage of PD-L1 positive samples at clinically relevant CPS ≥1, ≥5 and ≥10 cut-offs (Table) for the 28-8 assay were approximately two-fold higher than that of the 22C3 (CPS≥1: 70.3% vs 49.4%, p&lt;0.001; CPS≥5: 29.1% vs 13.4%, p&lt;0.001; CPS≥10: 13.7% vs 7.0%, p=0.004). The mean CPS score on 28-8 assay was nearly double that of the 22C3 (6.39 ±14.5 vs 3.46±8.98, p&lt;0.001). At the clinically important CPS≥5 cut-off, there was only moderate concordance between the 22C3 and 28-8 assays. Conclusions: Our findings suggest that scoring PD-L1 CPS with the 28-8 assay may result in higher proportion of PD-L1 positivity and higher PD-L1 scores compared to assessment with the 22C3 and other assays. Clinically, this could lead to a larger number of patients eligible and approved for ICI therapy. If assays are viewed and used interchangeability, a substantial number of patients may be inaccurately denied or granted treatment with ICIs based on the assay chosen. As such, until stronger evidence of inter-assay concordance is found, we urge caution in treating the assays as equivalent.[Table: see text]
Gemcitabine-docetaxel in patients with relapsed high-grade osteosarcoma after first-line treatment with high-dose ifosfamide: A retrospective multicenter study.
Authors: Maria Grazia Pionelli, Sebastian Dorin Asaftei, Cristina Meazza, Alessandra Longhi, Angela Tamburini, Luca Coccoli, Alessandra Merlini, Celeste Cagnazzo, Tirtei Tirtei, Franca Fagioli
Journal: Journal of Clinical Oncology (2022)

11520 Background: Currently, there is no accepted standard chemotherapy regimen for recurrent osteosarcoma. We performed a retrospective study to evaluate the effectiveness, toxicity and clinical benefit of second line therapy with Gemcitabine (G) in combination with Docetaxel (D), in patients with relapsed high-grade osteosarcoma who have been previously treated with High-dose Ifosfamide (HD-IFO) during first-line treatment (ClinicalTrials ID: NCT04651179). Methods: Patients were eligible to the analysis according to the following criteria: episode of first relapse of osteosarcoma, previous first line treatment according to poor responders’ arm of ISG-AIEOP OS 2 Protocol based on methotrexate, cisplatin, doxorubicin and HD-IFO (3gr/m2/day, day 1-5) ± Mifamurtide, presence of measurable disease according to RECIST 1.1, treatment with at least two cycles of Gemcitabine 900 mg/m2/day, days 1 and 8 and Docetaxel 75 mg/m2 day 8 every 21 days. Primary objective: overall survival (OS) at 12 months; secondary objectives: overall response rate (ORR) (complete response + partial response), progression-free survival (PFS) at 6-12 months, toxicity and quality of life. Results: 14 patients were included in the analysis. All patients were previously treated according to poor responders’ arm of ISG-AIEOP OS 2 Protocol, 7/14 (50%) of them received Mifamurtide. Most of patients (12/14, 86%) received 4 GD cycles and the total number of cycles administered was 60. Median OS was 20 months (range 11-69); OS at 12 and 24 months was 84% (95% CI 65-100) and 51% (95% CI 22-79), respectively; ORR were 35,7% after six cycles. Median PFS was 12 months (range 2-69); 6-months and 12-months PFS were 86% (95% CI 67-100) and 56% (30-83) respectively. For 8/14 (57%) patients a surgical approach was feasible after 2 and 6 GD cycles. Previous use of Mifamurtide correlate with a better 6-months PFS rate (100% vs 57%, P = 0.0011). Also, amelioration of ECOG/Lansky score showed a positive correlation with both PFS (P = 0.01) and OS (P = 0.04). No extra-hematological toxicities grade ≥3 was observed according to CTCAE v4.03 criteria. Conclusions: This trial confirms that GD combination has an anti-tumor activity for relapsed high-grade osteosarcoma with a well-tolerated toxicity profile. Furthermore, GD guarantee a surgical tumor remotion for patients with a chemo-resistant disease such as patients previously treated with a poor responders’ arm improving their OS and PFS rate. Promising results for patients previously treated with Mifamurtide need to be confirmed in future trials. Clinical trial information: NCT04651179.
Improved overall survival of metastatic cancers in the United States across all age groups in the immunotherapy era: Implications for considering elderly patients (age ≥ 75) for immune checkpoint inhibitors (ICIs).
Authors: Yu-Wei Chen, Matthew D Tucker, Hesham Abdallah Yasin, Xingyi Guo, Xiao-Ou Shu, Brian I. Rini
Journal: Journal of Clinical Oncology (2022)

12039 Background: ICIs have changed the treatment paradigm in many cancer histologies. Population-level data regarding the impact of ICIs on the contemporary US cancer patients is scarce. In addition, elderly patients were underrepresented in the landmark trials. Methods: Metastatic cancers (melanoma, lung cancer, kidney cancer, head and neck cancer, Hodgkin’s lymphoma, and urothelial cancer) diagnosed between 2004-2018 were identified in the Surveillance, Epidemiology, and End Results (SEER) database. The year of the first FDA approved ICI in each cancer site was considered the commencement of the ICI era. The impact of metastatic cancers diagnosed in the ICI era was assessed in each age group (&lt;65, 65-75, and ≥75) using multivariable Cox regression after adjustment for age, sex, race, household income and residence status (metropolitan vs non-metropolitan) Results: There were 363,191 patients with metastatic cancers included in the analysis [lung cancer: 68%, head and neck cancer: 14%, Hodgkin Lymphoma: 7%, kidney cancer: 7%, urothelial cancer: 3%, and melanoma: 2%): 60% were male and 73% were non-Hispanic White. The median age was 66 (interquartile range: 57-75). After baseline adjustments for sociodemographic factors, metastatic cancers diagnosed in the ICI era had improved overall survival except urothelial cancer (Table). Results of overall survival and cancer-specific survival were consistent across all age groups (&lt;65, 65-75, and ≥75). Among patients with age ≥75, metastatic cancers diagnosed in the ICI era had improved overall survival in melanoma (AHR: 0.81, p-value&lt;.0001), lung cancer (AHR:0.91, p-value&lt;.0001), kidney cancer (AHR: 0.89, p-value: 0.0004), head and neck cancer (AHR:0.82, p-value&lt;.0001), Hodgkin lymphoma (AHR: 0.75, p-value:0.003) but not in urothelial cancer. Conclusions: Metastatic cancers diagnosed in the ICI era had improved overall survival and cancer-specific survival including the subgroup of age ≥ 75. ICIs should not be withheld in elderly patients solely due to chronological age. [Table: see text]
Prevalence of high tumor mutational burden (TMB-H) and microsatellite instability-high (MSI-H) status in neuroendocrine neoplasms.
Authors: Sukhmani Kaur Padda, Rahul Raj Aggarwal, Arya Ashok, Elizabeth Mauer, Maryam Shirazi, Emily K. Bergsland
Journal: Journal of Clinical Oncology (2022)

2625 Background: Neuroendocrine neoplasms (NENs) encompass a rare group of tumors arising in nearly any organ site. Patients with advanced-stage NENs have limited treatment options, and molecular profiling is not routinely performed in NENs. However, given tissue-agnostic FDA approvals for immunotherapy in biomarker-selected solid tumors, we sought to assess the frequency of TMB-H and MSI-H in NENs by organ site and in comparison to non-NEN counterparts. Methods: We retrospectively analyzed de-identified records from the Tempus database of NENs sequenced with the Tempus xT assay (DNA-seq of 595-648 genes at 500x coverage). Patients were included if their primary cancer arose in the lungs, GI tract (esophagus, stomach, small bowel, colon, rectum), pancreas, or prostate. Histologic diagnoses were grouped as NENs (including high grade or low/intermediate grade), and non-NENs (e.g. adenocarcinoma, squamous cell carcinoma) based on data abstracted from pathology reports. TMB-H was defined as ≥ 10 mutations/megabase. MSI-H was calculated as previously published (PMID: 31570899). Statistical comparisons were limited to groups of 10 or larger. Results: We characterized a total of 1,477 NENs from the following anatomic sites: lung (64%, N=951), pancreas (15%, N= 220), GI (15%, N= 224) and prostate (6%, N=82). TMB-H was most common in NENs arising in the lungs (17%, N=155), followed by the pancreas (5.4%, N=11), GI tract (4.8%, N=10), and prostate (3.8%, N=3) (p&lt; 0.001). Overall, TMB-H was more common in high-grade NENs compared to low/int-grade NENs [17% (N=147) vs. 6.2% (N=31), P&lt;0.001]. This was also observed in lung NENs [high-grade 19% (N=135) v low/int grade 10% (N=19), P=0.006], with other organ site analyses limited by sample size (although a similar trend was noted for GI NENs). The majority of patients with TMB-H lung NENs had a current or prior smoking history (94%, N=119). Overall, TMB-H was similar in NENs compared to non-NENs [13% (N=179) vs. 12% (N=3018), P=0.4]. However, in the pancreas, TMB-H was more common in NENs vs. non-NENs [(5.4% (N=11) v 1.6% (N=59), P&lt;0.001] while the reverse was true in lung NENs [17% (N=155) v 22% (N=2006), P=0.001]. MSI-H was observed in only 0.9% (N=12) of NENs overall, including in 0.4% (N=4) of lung, 1.4% (N=3) of pancreas, 1.9% (N=4) of GI, and 1.2% (N=1) of prostate NENs. MSI-H status was less common in NENs compared to non-NENs [0.9% (N=12) vs. 2.5% (N=614), P&lt;0.001]. Conclusions: In this real-world NEN cohort, the actionable molecular alterations of TMB-H (13%) and MSI-H (0.9%) were observed. Taken together, the data suggest that molecular profiling (regardless of grade) may help identify a small but meaningful subset of patients with NENs who may benefit from immunotherapeutic treatment approaches. Furthermore, the identification of MSI-H NENs has important implications related to germline testing.
Associations between global longitudinal strain (GLS), N-terminal-prohormone brain natriuretic peptide (NT-proBNP) and subsequent cardiomyopathy (CM) in a clinically assessed cohort of childhood cancer survivors exposed to cardiotoxic therapy.
Authors: Matthew J. Ehrhardt, Qi Liu, John L. Jefferies, Daniel A. Mulrooney, Yadav Sapkota, Jason Goldberg, Stephanie B Dixon, John Thomas Lucas, Kirsten K. Ness, Deo Kumar Srivastava, Wojciech Mazur, Juan Carlos Plana Gomez, Leslie L. Robison, Yutaka Yasui, Melissa M. Hudson, Gregory T. Armstrong
Journal: Journal of Clinical Oncology (2022)

10052 Background: Among survivors exposed to anthracycline or chest radiation (RT) who have an ejection fraction (EF) of ≥50%, the utility of GLS and NT-proBNP to identify survivors who are at highest risk for future CM is unknown. Methods: Survivors participating in the St. Jude Lifetime Cohort, ≥5 years from cancer diagnosis and at risk for CM per the International Guideline Harmonization Group (IGHG), underwent baseline surveillance echocardiography. A baseline GLS and NT-proBNP was also performed for survivors with an EF ≥50%. Multivariable Cox regression models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for risk of CM (graded per modified Common Terminology Criteria for Adverse Events v4.0) based on abnormal baseline GLS (≥ -18) and/or NT-proBNP (&gt;age-sex-specific 97.5th percentiles) adjusted for age at baseline assessment, age at diagnosis, sex, race, hypertension, diabetes, obesity, and IGHG risk group (Table footnote). Results: Among 1598 at-risk survivors (median age 35.1, range 9.4-68.8 years), all had GLS and 1110 NT-proBNP at baseline. 165 (10.3%) developed CM ≥ grade 2 at a median follow-up of 5.2 (0.7-10.0) years. IGHG moderate- and high-risk survivors exposed to anthracyclines were at increased risk of CM at follow-up if both baseline GLS and NT-proBNP were abnormal (HR=3.4, 95% CI: 1.9-5.8; Table) or GLS was abnormal and NT-proBNP not assessed (HR=3.8, 95% CI: 2.0-7.2), or when GLS was normal and NT-proBNP was abnormal (HR=1.9, 95% CI: 1.1-3.4). Abnormal GLS and/or NT-proBNP were not associated with increased risk of CM in IGHG low-risk survivors or in those defined as moderate- to high-risk due to chest RT only. Conclusions: Among long-term survivors of childhood cancer exposed to &gt;100 mg/m 2 anthracycline, abnormal GLS and NT-proBNP identified those survivors at increased risk of future CM despite an EF ≥50% on surveillance echocardiography. Conditional surveillance strategies utilizing GLS and NT-proBNP may benefit moderate- to high-risk survivors. [Table: see text]
Long-term toxicities with immune checkpoint inhibitor (ICI) in melanoma patients.
Authors: Justin Tong, B. Adi Kartolo, Cynthia Yeung, Wilma M. Hopman, Tara D. Baetz
Journal: Journal of Clinical Oncology (2022)

e21549 Background: The incorporation of ICI into the treatment of melanoma has greatly improved patient outcomes, but this benefit has come at the cost of exposing patients to immune-related adverse events (irAEs). A wide spectrum of irAE types has been described, and severity is known to vary from minor to life-threatening; however, the literature to date on the chronicity of irAEs is limited. Objectives: To characterize the long-term and permanent irAEs associated with ICI treatment in patients with melanoma, the treatment of irAEs and the association with survival outcomes. Methods: We performed a retrospective chart review of 161 adult patients with melanoma treated with at least one cycle of ICI regimen in the adjuvant or metastatic setting: 129 patients received PD-1 inhibitor monotherapy and 32 received dual immunotherapy. Patients were grouped by duration of irAE: permanent (no complete resolution), long-term (resolution over a period ≥6 months), transient (resolution over a period &lt; 6 months), or no irAEs. Overall survival was evaluated for those patients that were treated in the metastatic setting with PD1 inhibitor monotherapy. Results: Thirty-eight patients were treated in the adjuvant setting and 123 patients were treated in the metastatic setting. A total of 279 irAEs were reported in the whole patient population. Sixty-six (41.0%) patients developed permanent irAEs, 15 (9.3%) experienced long-term irAEs as their longest-lasting toxicity, 34 (21.1%) developed transient irAEs only, and 46 (28.6%) experienced no irAEs. Permanent irAEs occurred in 21 (65.6%) patients treated with dual immunotherapy and in 45 (34.9%) patients treated with monotherapy. The majority of permanent irAEs were endocrine-related (35.5%) or skin-related (32.7%). Grade ≥3 permanent irAEs occurred in 20 (12.4%) patients and included toxicities such as adrenal insufficiency, myocarditis, and myelitis. Fifty-three (32.9%) patients were still on treatment for long-term or permanent irAEs 6 months or more following completion of ICI therapy, including 23 patients on thyroid replacement and 22 on oral steroids. ICI treatment was temporarily interrupted for 63 (22.6%) irAEs and permanently discontinued due to irAE in 38 (13.6%) patients. Subgroup analysis of patients who received single-agent ICI in the first-line palliative setting reveals that those with longer-duration irAEs had a significantly longer median overall survival. Conclusions: Despite the significant benefits, treatment with ICIs in melanoma is associated with a wide range of toxicities that can be permanent and may have long-lasting impacts on patients. The risk of long-term toxicity should therefore be discussed when obtaining consent for treatment. As these treatments are being used more commonly in the adjuvant setting, the impact of survivorship and the long-term management of these toxicities is increasingly important.
The role of health information technology in improving awareness of HPV and HPV vaccine among U.S. adults: Insights from the health information national trends survey.
Authors: Gideon T Dosunmu, Henry Onyeaka, Emmanuel Kyeremeh, Mohammed Jalwa, Emmanuella Onaku, Jillian Ofori, Hermioni L. Amonoo, Muhammmad Areeb Ashfaq, Moh'd M. Khushman
Journal: Journal of Clinical Oncology (2022)

10535 Background: Despite advances in cancer prevention and wide-spread availability of Human papilloma virus (HPV) vaccines, US adults continue to have suboptimal HPV vaccination uptake with less than 50% vaccinated. Strategies aimed at enhancing HPV-related awareness are considered one of the most effective ways to improve HPV vaccine adoption and potentially eliminate HPV-related cancers. Health information technology (HIT) may influence HPV-related awareness and subsequently drive vaccine adoption. This study assessed the impact of HIT utilization on HPV and HPV vaccine awareness. Methods: Data was obtained from Health Information National Trends Survey (HINTS 5 cycles 1 and 2). Cross-sectional sample of 6,522 individuals aged 18 years or more was analyzed. The independent variables were use of smartphone, computer, or electronic means to (i) look up health information, (ii) fill a prescription online, (iii) communicate with a doctor or doctor’s office, (iv) look up test results of and (v) track health care charges. The dependent variables were HPV and HPV vaccine awareness. Chi-square analysis was used to evaluate group differences, and a multiple logistic regression was used to analyze the association between HIT utilization and HPV-related awareness controlling for sociodemographic and health-related factors. Results: Of the total sample, awareness of HPV and HPV vaccine was 62.7% and 61.8% respectively. In adjusted multivariable logistic regression analysis, those who utilized a smartphone, computer, or electronic means to look up health information (aOR 2.23; 95% CI 1.68 – 2.97, p &lt; 0.001), communicate with healthcare provider (aOR 1.53; 95% CI 1.23 – 1.91, p &lt; 0.001), look up test results (aOR 1.67; 95% CI 1.35 – 2.08, p &lt; 0.001), and track health care charges (aOR 1.61; 95% CI 1.26 – 2.05, p &lt; 0.001), were more likely to endorse HPV awareness than those who did not. Similar positive associations were observed for HIT utilization and HPV vaccine awareness. Conclusions: Our findings showed a positive association between HIT utilization and HPV-related awareness. Amid a background of sub-optimal HPV vaccination and explosion in technology, these results emphasize the potential for the role of HIT in preventive medicine. Strategies that integrate HIT into vaccine interventions and communications should be encouraged as a medium to expand HPV awareness and vaccine coverage.
Development of blood components samples collection as a source for new biomarkers search in multiple myeloma.
Authors: Nadezhda V. Gnennaya, Oleg I. Kit, Svetlana Yu Filippova, Anastasia O. Sitkovskaya, Irina V. Mezhevova, Tatiana V. Shamova, Sofia V. Timofeeva, Inna A. Novikova, Irina B. Lysenko, Nadezhda V. Nikolaeva, Natalia Yu. Samaneva, Yakha S. Gaysultanova, Inna A. Kamaeva, Anna V. Tishina, Tatiana F. Pushkareva, Elena A. Kapuza
Journal: Journal of Clinical Oncology (2022)

e15009 Background: Multiple myeloma (MM) is a B-cell malignancy resulting from the abnormal proliferation of neoplastic plasma cells that produce monoclonal immunoglobulin (Ig). The high variability of the course of this disease, its genetic clonal heterogeneity, is due to chromosomal deletions, chromosomal hyperploidy involving an odd number of chromosomes, as well as genetic aberrations, such as rearrangement of the Ig heavy chain gene loci. Since the available biomarkers do not take into account this feature of MM, there is a need to develop more advanced biomarkers that will more accurately predict the course of the disease and response to treatment. Methods: The collection of MM samples included biological samples obtained from patients over 18 years of age with a diagnosis of MM, who received treatment in the National Medical Research Center of Oncology since 2019. Only patients who signed an informed consent for the use of their biomaterial for scientific purposes were included in the project. The material was collected according to the developed algorithm of clinical information and biological material collection, sample preparation, quality control and storage in the cryostorage of the National Medical Research Centre for Oncology of the Ministry of Health of Russia (Rostov-on-Don). Results: As of December 23, 2021, collection consists of 387 samples of whole blood, serum, plasma and mononuclear cells obtained from 42 MM patients of both sexes, whose average age was 59.7 ± 1.49 (±SD) years. Each patient was assigned a unique identification number. Freezing of the obtained samples occurred in accordance with the low-temperature storage protocol. Registration, accounting and certification of the material were carried out in a specialized database for recording and storing information about biological samples. Conclusions: The identification of MM biomarkers is important for increasing the sensitivity of molecular monitoring, which makes it possible to stratify patients into risk groups for early relapses and treatment resistance development. Thanks to the accumulated experience, the Biobank of the National Medical Research Centre for Oncology of the Ministry of Health of Russia serves as a valuable resource for providing research in the development of new predictive molecular markers.